Universität zu Köln

Kmietczyk, Vivien, Riechert, Eva ORCID: 0000-0003-4876-7860, Kalinski, Laura, Boileau, Etienne, Malovrh, Ellen ORCID: 0000-0003-0911-6125, Malone, Brandon, Gorska, Agnieszka, Hofmann, Christoph ORCID: 0000-0002-3389-6582, Varma, Eshita, Juergensen, Lonny, Kamuf-Schenk, Verena, Altmueller, Janine, Tappu, Rewati, Busch, Martin, Most, Patrick, Katus, Hugo A., Dieterich, Christoph and Voelkers, Mirko (2019). m(6)A-mRNA methylation regulates cardiac gene expression and cellular growth. Life Sci. Alliance, 2 (2). COLD SPRING HARBOR: LIFE SCIENCE ALLIANCE LLC. ISSN 2575-1077

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Abstract

Conceptually similar to modifications of DNA, mRNAs undergo chemical modifications, which can affect their activity, localization, and stability. The most prevalent internal modification in mRNA is the methylation of adenosine at the N-6-position (m(6)A). This returns mRNA to a role as a central hub of information within the cell, serving as an information carrier, modifier, and attenuator for many biological processes. Still, the precise role of internal mRNA modifications such as m(6)A in human and murine-dilated cardiac tissue remains unknown. Transcriptome-wide mapping of m(6)A in mRNA allowed us to catalog m(6)A targets in human and murine hearts. Increased m(6)A methylation was found in human cardiomyopathy. Knockdown and overexpression of the m(6)A writer enzyme Mettl3 affected cell size and cellular remodeling both in vitro and in vivo. Our data suggest that mRNA methylation is highly dynamic in cardiomyocytes undergoing stress and that changes in the mRNA methylome regulate translational efficiency by affecting transcript stability. Once elucidated, manipulations of methylation of specific m(6)A sites could be a powerful approach to prevent worsening of cardiac function.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kmietczyk, Vivien UNSPECIFIED UNSPECIFIED UNSPECIFIED Riechert, Eva UNSPECIFIED orcid.org/0000-0003-4876-7860 UNSPECIFIED Kalinski, Laura UNSPECIFIED UNSPECIFIED UNSPECIFIED Boileau, Etienne UNSPECIFIED UNSPECIFIED UNSPECIFIED Malovrh, Ellen UNSPECIFIED orcid.org/0000-0003-0911-6125 UNSPECIFIED Malone, Brandon UNSPECIFIED UNSPECIFIED UNSPECIFIED Gorska, Agnieszka UNSPECIFIED UNSPECIFIED UNSPECIFIED Hofmann, Christoph UNSPECIFIED orcid.org/0000-0002-3389-6582 UNSPECIFIED Varma, Eshita UNSPECIFIED UNSPECIFIED UNSPECIFIED Juergensen, Lonny UNSPECIFIED UNSPECIFIED UNSPECIFIED Kamuf-Schenk, Verena UNSPECIFIED UNSPECIFIED UNSPECIFIED Altmueller, Janine UNSPECIFIED UNSPECIFIED UNSPECIFIED Tappu, Rewati UNSPECIFIED UNSPECIFIED UNSPECIFIED Busch, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Most, Patrick UNSPECIFIED UNSPECIFIED UNSPECIFIED Katus, Hugo A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Dieterich, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Voelkers, Mirko UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-151780
DOI:	10.26508/lsa.201800233
Journal or Publication Title:	Life Sci. Alliance
Volume:	2
Number:	2
Date:	2019
Publisher:	LIFE SCIENCE ALLIANCE LLC
Place of Publication:	COLD SPRING HARBOR
ISSN:	2575-1077
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MESSENGER-RNA TRANSLATION; NUCLEAR-RNA; HEART; N-6-METHYLADENOSINE; DIFFERENTIATION; PROTECTS; MUSCLE; MODEL; LINE Multiple languages Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/15178